Over the last decade it has become increasingly recognized that non-malignant components of a tumor, called the tumor microenvironment (TME), play a major contributor role in cancer development and progression 1-4. This heterotypic view of cancer recognizes that tumor cells which may not be intrinsically able to disseminate or to resist therapeutic insults, can acquire these properties as the result of specific interactions with the microenvironment. Physical microenvironmental conditions such as hypoxia and acidosis 5, adhesion to the extracellular matrix (ECM) 6, growth factors, pro-inflammatory cytokines and chemokines 7, carcinoma- associated fibroblasts and endothelial cells, innate and adaptative immune cells and tumor-associated macrophages contribute to all stages of cancer progression from malignant transformation to metastasis and resistance to therapy. After having a primary focus on the extracellular matrix (ECM) and on angiogenesis in the late 1990's, our knowledge of the mechanisms by which the microenvironment affects tumor progression has grown at an exponential rate. We appreciate better the complexity of the tumor microenvironment and its role in cancer progression and have seen many new concepts emerging (Figure 1). For example, it is well demonstrated that bone marrow-derived cells contribute to tumor vasculogenesis and to the establishment of the pro-metastatic niche. We now fully realize that the immune system can be polarized in a manner that suppresses or promotes cancer progression and that macrophages play an essential role in metastasis. We understand better the mechanism by which the tumor microenvironment promotes therapeutic resistance 8. It is therefore a particularly exciting time in this field, as our knowledge reaches the critical point when it begins to translate into new therapeutic modalities. In this application we are requesting support for a conference on Tumor Microenvironment Complexity: Emerging Roles in Cancer Therapy to be held November 3-6, 2011 at the Hilton Orlando Hotel, Orlando, FL. PUBLIC HEALTH RELEVANCE: As we begin to understand how the tumor microenvironment can influence tumor initiation, progression, metastasis, and resistance to therapy, we are better equipped to utilize this knowledge for translation into new therapeutic modalities. The purpose of this timely conference is to bring together experts in the field and more junior scientists to discuss these emerging concepts, to examine their translational importance, and to identify other areas in the field that should be the focus of further investigation.